Is CHPF p.Ser48Pro (c.142T>C) pathogenic?

CHPF p.Ser48Pro (c.142T>C) is classified Benign/Likely benign in CHPF (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-18). AlphaMissense: likely benign (0.0573); Low-frequency (popmax 2.83%, afr).

How common is CHPF p.Ser48Pro (c.142T>C) in the general population?

CHPF p.Ser48Pro (c.142T>C) is low-frequency (popmax 2.83%, afr) (gnomAD).

What do computational predictors say about CHPF p.Ser48Pro (c.142T>C)?

AlphaMissense predicts likely benign (score 0.0573) — an in-silico prediction, not a clinical call.

CHPF p.Ser48Pro

c.142T>C · rs61733622 · VCV791892

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0573 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.83%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0573	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -5.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 1.5, phastCons 0.97
Regional constraint	o/e 0.88	unconstrained · MANE · 4,044 bp · p 0.00017 · regional, not allelic
Overall
CADD	16.37	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.83% African / African-American · 2,002/70,796 alleles

Filtering AF 2.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.68%

Overall 0.152% 2,369/1,558,906 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.83%	35
Middle Eastern	0.276%	362
Remaining individualsnot grpmax-eligible	0.225%	445
Admixed American	0.209%	479
South Asian	0.0208%	4,804
European (non-Finnish)	0.00688%	14,532
Finnishnot grpmax-eligible	0.00212%	47,248

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CHPF
Protein: p.Ser48Pro
Coding: c.142T>C
MANE Select: NM_024536
dbSNP: rs61733622
Type: single nucleotide variant
Location: chr2:219543397 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.57 · 2 PDB
Residue 48: the 'disordered' region

Full CHPF gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHPF p.Glu699= Benign ★★ same type
CHPF p.Ala206Ser Uncertain significance ★ ⚠ same type
CHPF p.Ala286Val Uncertain significance ★ ⚠ same type
CHPF p.Ala341Thr Uncertain significance ★ ⚠ same type
CHPF p.Ala343Gly Uncertain significance ★ ⚠ same type
CHPF p.Ala516Val Uncertain significance ★ ⚠ same type
CHPF p.Ala530Gly Uncertain significance ★ ⚠ same type
CHPF p.Ala539Val Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/chpf-p-ser48pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown